YIJOM-2829; No of Pages 5
Int. J. Oral Maxillofac. Surg. 2014; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2013.12.003, available online at http://www.sciencedirect.com
Case Report Head and Neck Oncology
Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma
D. Tighe, S. Cavilla, R. Simcock Royal Sussex County Hospital, Brighton, East Sussex, UK
D. Tighe, S. Cavilla, R. Simcock: Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma. Int. J. Oral Maxillofac. Surg. 2014; xxx: xxx–xxx. # 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Pulmonary lymphangitic carcinomatosis (PLC) secondary to mucosal head and neck squamous cell carcinoma (HNSCC) is extremely rare, difficult to diagnose in the pre-symptomatic phase, and is rapidly fatal. We describe two cases of fatal PLC secondary to squamous cell carcinoma in whom a review of pre-treatment imaging (computed tomography of the chest) changes reported as unspecific were retrospectively felt to be consistent with pre-symptomatic PLC. Case 1, a 73-yearold male with T2N2bMx poorly differentiated squamous cell carcinoma of the right tonsil, died 6 weeks after chemoradiotherapy with curative intent. Case 2, a 65-yearold female with T4aN2bMx of the right body of the mandible, died within 6 weeks of radical surgery including free tissue transfer. A review of the literature showed that PLC secondary to HNSCC occurs in an older cohort of patients: mean age 69 years vs. other tumour groups 50 years. PLC secondary to HNSCC can behave in distinctly different ways, demonstrating similarity to either gastric adenocarcinoma or bronchogenic squamous cell carcinomas.
Introduction
Pulmonary lymphangitic carcinomatosis (PLC) secondary to mucosal head and neck squamous cell carcinoma (HNSCC) is extremely rare, difficult to diagnose in the pre-symptomatic phase, and is rapidly fatal. We aim to increase awareness of this disease entity in the speciality of Head and Neck, as both cases we discuss had unspecific changes noted on pre-treatment staging computed tomography (CT) of the chest that were not further investigated. A literature review of PLC follows a discussion of two recent cases of PLC in our head and neck unit who died of respiratory 0901-5027/000001+05 $36.00/0
failure secondary to PLC within 6 weeks of receiving radical treatment with curative intent for HNSCC.
Case reports Case 1
A 73-year-old man presented with a 2month history of odynophagia and right neck swelling. He was an ex-smoker who had not consumed alcohol for many years. Staging magnetic resonance imaging (MRI), panendoscopy, and biopsy revealed a T2N2bMx poorly differentiated cancer of the right tonsil. A chest CT
Key words: pulmonary lymphangitic carcinomatosis; squamous cell carcinoma. Accepted for publication 18 December 2013
(standard protocol 5-mm cuts; Fig. 1) showed some small nodules and ground glass opacities. At multidisciplinary review, these were considered likely to be benign changes. No distant metastases were seen. The patient received intensity modulated radiotherapy at 65 Gy in 30 fractions to the right neck nodal levels 2–4 with concomitant cetuximab 400 mg/m2 week 1, then 250 mg/m2 week 2. The cetuximab was stopped due to marked mucosal and cutaneous toxicity and dehydration requiring admission. A radiologically inserted gastrostomy was inserted during radiotherapy to support nutrition. There were
# 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tighe D, et al. Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma, Int J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.ijom.2013.12.003
YIJOM-2829; No of Pages 5
2
Tighe et al.
Fig. 3. Case 1, CT pulmonary angiogram: features of lymphangitic carcinomatosis. Fig. 1. Case 1, pre-treatment staging CT.
no missed fractions of radiotherapy in the radical course. At outpatient review 6 weeks later the patient reported breathlessness with chest pain and a non-productive cough for 4 weeks unresponsive to oral antibiotics. At review the patient was tachypnoeic, hypoxic, and had a loud second heart sound, widespread wheeze, and crackles. Features of fluid overload were absent. A provisional diagnosis of communityacquired pneumonia prompted admission for oxygen therapy and intravenous broadspectrum antibiotics. Therapeutic anticoagulation with low molecular weight heparin was administered pending a CT pulmonary angiogram (CTPA). Admission blood tests showed a normal white blood cell count (WBC) of 9.9 109/ l (slight neutrophilia 8.2 109/l and lymphopaenia 0.5 109/l) and a C-reactive protein (CRP) of 67.5 mg/l. Admission arterial blood gases showed a partial pressure of oxygen (pO2) of 7.8 mmHg off oxygen. The electrocardiogram showed sinus tachycardia, left anterior fascicular block, and premature supraventricular beats. D-dimers were not requested. The chest X-ray (Fig. 2) demonstrated widespread nodular shadowing and a pleural effusion.
Fig. 2. Case 1, admission chest X-ray.
A subsequent CTPA (fine cut, 1.5-mm) (Fig. 3) revealed features of lymphangitic carcinomatosis: widespread nodules and extensive miliary shadowing with enlarged nodes that had progressed rapidly. As PLC is not commonly observed in head and neck cancers, a pleural tap for cytology was performed, confirming the presence of a central cluster of poorly differentiated carcinoma cells in a background of reactive mesothelial cells, lymphocytes, and granulocytes (Fig. 4). The patient initially improved with high-dose dexamethasone and oxygen, but unfortunately 10 days later he developed increasingly severe hypoxia and respiratory distress, and with further palliation of symptoms, died that night. Case 2
A 65-year-old female who was fit and independent presented with a 6-week history of right-sided odynophagia. She was an ex-smoker and had occasional alcohol intake. She had a past history of oestrogen receptor-positive breast cancer first diagnosed in December 1998. This was treated with breast-conserving surgery, chemotherapy, adjuvant radiotherapy, and tamoxifen. A nodal recurrence 3 years later in the left supraclavicular fossa was treated with radiotherapy and aromatase inhibitors. A further nodal recurrence later that year was treated with chemotherapy, achieving remission. She was on
Fig. 4. Case 1, cytology of pleural tap.
thyroid replacement therapy. Staging MRI and biopsy revealed a T4aN1Mx moderately differentiated carcinoma arising within a field of severe dysplasia on the right retromolar trigone of the mandible. Her staging CT showed numerous suspicious right-sided cervical lymph nodes involving the supraclavicular, submandibular, and internal jugular regions, with no evidence of visceral distant metastases (Fig. 5). The patient underwent a segmental mandibulectomy, selective neck dissection of the ipsilateral side, tracheostomy, and reconstruction with a composite fibula free flap. Concern during surgery about nodal disease prompted frozen sections of the right supraclavicular nodes, which confirmed the presence of carcinoma. After an overnight stay in the intensive therapy unit (ITU), ventilated and sedated to protect the microvascular anastomosis, she was easily weaned from the ventilator and transferred to the ward on routine thromboprophylaxis. Good progress continued allowing decannulation of the tracheostomy tube on day 7. Histology confirmed a T4aN2bMx moderately differentiated squamous cell carcinoma demonstrating perineural and vascular invasion with clear margins; 58/74 nodes showed tumour, the largest deposit at 25 mm. Mild dyspnoea and a cough productive of yellow sputum associated with a leukocytosis of 16 109/l on days 8–9 prompted a diagnosis of hospital-acquired pneumonia for which she was started on meropenem and teicoplanin. The chest Xray taken on day 9 is shown in Fig. 6. There was no temperature spike. She continued to develop type 1 respiratory failure, and auscultation revealed fine crepitations throughout the lung fields. The cough became unproductive and she had an increasing oxygen requirement unresponsive to chest physiotherapy, nebulized saline, and antibiotics. On day 11, a chest CTPA excluded a pulmonary
Fig. 5. Case 2, pre-treatment staging CT.
Please cite this article in press as: Tighe D, et al. Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma, Int J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.ijom.2013.12.003
YIJOM-2829; No of Pages 5
Pulmonary lymphangitic carcinomatosis
3
including one other from the tonsil, as we have reported here. Definition
Fig. 6. Case 2, day 9 chest X-ray.
embolism but showed bilateral pleural effusions and right basal consolidation. A chest drain was inserted the following day and removed 24 h later. She had a Mycoplasma false-positive titre of 320, but repeat testing the following day showed a result of
Int. J. Oral Maxillofac. Surg. 2014; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2013.12.003, available online at http://www.sciencedirect.com
Case Report Head and Neck Oncology
Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma
D. Tighe, S. Cavilla, R. Simcock Royal Sussex County Hospital, Brighton, East Sussex, UK
D. Tighe, S. Cavilla, R. Simcock: Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma. Int. J. Oral Maxillofac. Surg. 2014; xxx: xxx–xxx. # 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Pulmonary lymphangitic carcinomatosis (PLC) secondary to mucosal head and neck squamous cell carcinoma (HNSCC) is extremely rare, difficult to diagnose in the pre-symptomatic phase, and is rapidly fatal. We describe two cases of fatal PLC secondary to squamous cell carcinoma in whom a review of pre-treatment imaging (computed tomography of the chest) changes reported as unspecific were retrospectively felt to be consistent with pre-symptomatic PLC. Case 1, a 73-yearold male with T2N2bMx poorly differentiated squamous cell carcinoma of the right tonsil, died 6 weeks after chemoradiotherapy with curative intent. Case 2, a 65-yearold female with T4aN2bMx of the right body of the mandible, died within 6 weeks of radical surgery including free tissue transfer. A review of the literature showed that PLC secondary to HNSCC occurs in an older cohort of patients: mean age 69 years vs. other tumour groups 50 years. PLC secondary to HNSCC can behave in distinctly different ways, demonstrating similarity to either gastric adenocarcinoma or bronchogenic squamous cell carcinomas.
Introduction
Pulmonary lymphangitic carcinomatosis (PLC) secondary to mucosal head and neck squamous cell carcinoma (HNSCC) is extremely rare, difficult to diagnose in the pre-symptomatic phase, and is rapidly fatal. We aim to increase awareness of this disease entity in the speciality of Head and Neck, as both cases we discuss had unspecific changes noted on pre-treatment staging computed tomography (CT) of the chest that were not further investigated. A literature review of PLC follows a discussion of two recent cases of PLC in our head and neck unit who died of respiratory 0901-5027/000001+05 $36.00/0
failure secondary to PLC within 6 weeks of receiving radical treatment with curative intent for HNSCC.
Case reports Case 1
A 73-year-old man presented with a 2month history of odynophagia and right neck swelling. He was an ex-smoker who had not consumed alcohol for many years. Staging magnetic resonance imaging (MRI), panendoscopy, and biopsy revealed a T2N2bMx poorly differentiated cancer of the right tonsil. A chest CT
Key words: pulmonary lymphangitic carcinomatosis; squamous cell carcinoma. Accepted for publication 18 December 2013
(standard protocol 5-mm cuts; Fig. 1) showed some small nodules and ground glass opacities. At multidisciplinary review, these were considered likely to be benign changes. No distant metastases were seen. The patient received intensity modulated radiotherapy at 65 Gy in 30 fractions to the right neck nodal levels 2–4 with concomitant cetuximab 400 mg/m2 week 1, then 250 mg/m2 week 2. The cetuximab was stopped due to marked mucosal and cutaneous toxicity and dehydration requiring admission. A radiologically inserted gastrostomy was inserted during radiotherapy to support nutrition. There were
# 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tighe D, et al. Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma, Int J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.ijom.2013.12.003
YIJOM-2829; No of Pages 5
2
Tighe et al.
Fig. 3. Case 1, CT pulmonary angiogram: features of lymphangitic carcinomatosis. Fig. 1. Case 1, pre-treatment staging CT.
no missed fractions of radiotherapy in the radical course. At outpatient review 6 weeks later the patient reported breathlessness with chest pain and a non-productive cough for 4 weeks unresponsive to oral antibiotics. At review the patient was tachypnoeic, hypoxic, and had a loud second heart sound, widespread wheeze, and crackles. Features of fluid overload were absent. A provisional diagnosis of communityacquired pneumonia prompted admission for oxygen therapy and intravenous broadspectrum antibiotics. Therapeutic anticoagulation with low molecular weight heparin was administered pending a CT pulmonary angiogram (CTPA). Admission blood tests showed a normal white blood cell count (WBC) of 9.9 109/ l (slight neutrophilia 8.2 109/l and lymphopaenia 0.5 109/l) and a C-reactive protein (CRP) of 67.5 mg/l. Admission arterial blood gases showed a partial pressure of oxygen (pO2) of 7.8 mmHg off oxygen. The electrocardiogram showed sinus tachycardia, left anterior fascicular block, and premature supraventricular beats. D-dimers were not requested. The chest X-ray (Fig. 2) demonstrated widespread nodular shadowing and a pleural effusion.
Fig. 2. Case 1, admission chest X-ray.
A subsequent CTPA (fine cut, 1.5-mm) (Fig. 3) revealed features of lymphangitic carcinomatosis: widespread nodules and extensive miliary shadowing with enlarged nodes that had progressed rapidly. As PLC is not commonly observed in head and neck cancers, a pleural tap for cytology was performed, confirming the presence of a central cluster of poorly differentiated carcinoma cells in a background of reactive mesothelial cells, lymphocytes, and granulocytes (Fig. 4). The patient initially improved with high-dose dexamethasone and oxygen, but unfortunately 10 days later he developed increasingly severe hypoxia and respiratory distress, and with further palliation of symptoms, died that night. Case 2
A 65-year-old female who was fit and independent presented with a 6-week history of right-sided odynophagia. She was an ex-smoker and had occasional alcohol intake. She had a past history of oestrogen receptor-positive breast cancer first diagnosed in December 1998. This was treated with breast-conserving surgery, chemotherapy, adjuvant radiotherapy, and tamoxifen. A nodal recurrence 3 years later in the left supraclavicular fossa was treated with radiotherapy and aromatase inhibitors. A further nodal recurrence later that year was treated with chemotherapy, achieving remission. She was on
Fig. 4. Case 1, cytology of pleural tap.
thyroid replacement therapy. Staging MRI and biopsy revealed a T4aN1Mx moderately differentiated carcinoma arising within a field of severe dysplasia on the right retromolar trigone of the mandible. Her staging CT showed numerous suspicious right-sided cervical lymph nodes involving the supraclavicular, submandibular, and internal jugular regions, with no evidence of visceral distant metastases (Fig. 5). The patient underwent a segmental mandibulectomy, selective neck dissection of the ipsilateral side, tracheostomy, and reconstruction with a composite fibula free flap. Concern during surgery about nodal disease prompted frozen sections of the right supraclavicular nodes, which confirmed the presence of carcinoma. After an overnight stay in the intensive therapy unit (ITU), ventilated and sedated to protect the microvascular anastomosis, she was easily weaned from the ventilator and transferred to the ward on routine thromboprophylaxis. Good progress continued allowing decannulation of the tracheostomy tube on day 7. Histology confirmed a T4aN2bMx moderately differentiated squamous cell carcinoma demonstrating perineural and vascular invasion with clear margins; 58/74 nodes showed tumour, the largest deposit at 25 mm. Mild dyspnoea and a cough productive of yellow sputum associated with a leukocytosis of 16 109/l on days 8–9 prompted a diagnosis of hospital-acquired pneumonia for which she was started on meropenem and teicoplanin. The chest Xray taken on day 9 is shown in Fig. 6. There was no temperature spike. She continued to develop type 1 respiratory failure, and auscultation revealed fine crepitations throughout the lung fields. The cough became unproductive and she had an increasing oxygen requirement unresponsive to chest physiotherapy, nebulized saline, and antibiotics. On day 11, a chest CTPA excluded a pulmonary
Fig. 5. Case 2, pre-treatment staging CT.
Please cite this article in press as: Tighe D, et al. Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma, Int J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.ijom.2013.12.003
YIJOM-2829; No of Pages 5
Pulmonary lymphangitic carcinomatosis
3
including one other from the tonsil, as we have reported here. Definition
Fig. 6. Case 2, day 9 chest X-ray.
embolism but showed bilateral pleural effusions and right basal consolidation. A chest drain was inserted the following day and removed 24 h later. She had a Mycoplasma false-positive titre of 320, but repeat testing the following day showed a result of
